Reduced immunogenicity of induced pluripotent stem cells derived from Sertoli cells.
Reduced immunogenicity of induced pluripotent stem cells derived from Sertoli cells.
复制标题
DOI：
10.1371/journal.pone.0106110
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zenke M
中科院分区：
文献类型：
--
作者：
Wang X;Qin J;Zhao RC;Zenke M
支持细胞构成睾丸的结构框架，为生殖细胞提供免疫优势环境。诱导多能干细胞(iPS细胞)类似于胚胎干细胞(ES细胞)，由体细胞通过表达特定的重编程转录因子而产生。在这里，我们使用C57BL/6(B6)Sertoli细胞产生iPS细胞(Ser-iPS细胞)，并比较了Ser-iPS细胞和小鼠胚胎成纤维细胞来源的iPS细胞(MEF-iPS细胞)的免疫原性。将Ser-iPS细胞注射到同基因小鼠体内，在畸胎瘤实验中检测其体内免疫原性。畸胎瘤试验可以同时评估iPS细胞及其分化后代的体内免疫原性。我们观察到，早期传代的Ser-iPS细胞比MEF-iPS细胞形成更多的畸胎瘤，免疫细胞浸润和组织损伤和坏死更少。与MEF-iPS细胞相比，在类胚体中分化的Ser-iPS细胞的T细胞激活潜能降低，这与同基因ES细胞相似。然而，Ser-iPS细胞在体外长时间传代后失去了体内降低的免疫原性，而后期传代的Ser-iPS细胞表现出与MEF-iPS细胞相似的免疫原性。这些结果表明，早期传代的SeriPS细胞保留了一些Sertoli细胞的躯体记忆，这影响了体内和体外iPS细胞和iPS细胞来源的细胞的免疫原性。我们的数据表明，如果将iPS细胞来源的细胞用于移植，免疫特权的Sertoli细胞可能是iPS细胞生成的首选来源。
Sertoli cells constitute the structural framework in testis and provide an immune-privileged environment for germ cells. Induced pluripotent stem cells (iPS cells) resemble embryonic stem cells (ES cells) and are generated from somatic cells by expression of specific reprogramming transcription factors. Here, we used C57BL/6 (B6) Sertoli cells to generate iPS cells (Ser-iPS cells) and compared the immunogenicity of Ser-iPS cells with iPS cells derived from mouse embryonic fibroblast (MEF-iPS cells). Ser-iPS cells were injected into syngeneic mice to test for their in vivo immunogenicity in teratoma assay. Teratoma assay allows assessing in vivo immunogenicity of iPS cells and of their differentiated progeny simultaneously. We observed that early-passage Ser-iPS cells formed more teratomas with less immune cell infiltration and tissue damage and necrosis than MEF-iPS cells. Differentiating Ser-iPS cells in embryoid bodies (EBs) showed reduced T cell activation potential compared to MEF-iPS cells, which was similar to syngeneic ES cells. However, Ser-iPS cells lost their reduced immunogenicity in vivo after extended passaging in vitro and late-passage Ser-iPS cells exhibited an immunogenicity similar to MEF-iPS cells. These findings indicate that early-passage Ser-iPS cells retain some somatic memory of Sertoli cells that impacts on immunogenicity of iPS cells and iPS cell-derived cells in vivo and in vitro. Our data suggest that immune-privileged Sertoli cells might represent a preferred source for iPS cell generation, if it comes to the use of iPS cell-derived cells for transplantation.
登录
查看更多内容
DOI：
10.1073/pnas.0404743101
发表时间：
2004-12-07
影响因子：
11.1
作者：
Ma, XP;Dong, YL;Kumar, TR
通讯作者：
Kumar, TR
影响因子：
64.5
作者：
Hanna, Jacob;Markoulaki, Styliani;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
3.6
作者：
Dal Secco, Valentina;Riccioli, Anna;Filippini, Antonio
通讯作者：
Filippini, Antonio
影响因子：
64.8
作者：
Guan, K;Nayernia, K;Hasenfuss, G
通讯作者：
Hasenfuss, G
iPSC 衍生的细胞可能具有免疫原性 - 是还是否？
影响因子：
21.1
作者：
Cao, Jiani;Li, Xiaoyan;Lu, Xiao;Zhang, Chao;Yu, Honghao;Zhao, Tongbiao
通讯作者：
Zhao, Tongbiao